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Epidemiology & Social

Adherence is not a barrier to successful antiretroviral therapy in South Africa

Orrell, Catherine; Bangsberg, David Ra; Badri, Motasim; Wood, Robin

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From the Diana, Princess of Wales HIV Research Unit, Somerset Hospital, University of Cape Town, South Africa, and the aEpidemiology and Prevention Interventions Centre, Division of Infectious Diseases and the Positive Health Program, UCSF, San Francisco, California, USA.

Correspondence to C. Orrell, Diana, Princess of Wales HIV Research Unit, PO Box 50309, V & A Waterfront, Cape Town, South Africa, 8005.

Note: Presented in part at the International AIDS Society Conference, Buenos Aires, July 2001 [abstract 696] and at the XIV International Conference on AIDS, Barcelona, July 2002 [abstract WePeB5816].

Received: 16 August 2003; revised: 20 December 2003; accepted: 22 January 2003.

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Objective: to determine adherence of an indigent African HIV-infected cohort initiating antiretroviral therapy (ART); to identify predictors of incomplete adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml).

Design: Prospective monitoring of adherence in a poor HIV-positive cohort, attending a public sector hospital and receiving ART through phase III studies.

Methods: Adherence to ART was determined over 48 weeks by counting tablet-returns. Logistic regression models including age, WHO HIV stage, home language, socio-economic status, complexity and type of regimen were fitted to determine predictors of incomplete adherence and virologic failure at 48 weeks.

Results: 289 patients were recruited between January 1996 and May 2001. Median (mean) adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio (RR), 3.07; 95% confidence interval (CI), 1.40–6.74], speaking English (RR, 0.41; 95% CI, 0.21–0.80) and age (RR, 0.97; 95% CI, 0.94–0.99) were independent predictors of incomplete adherence. Socio-economic status, sex and HIV stage did not predict adherence. Independent predictors of virologic failure included baseline viral load (RR, 2.57; 95% CI, 1.57–4.22) and three times daily dosing (RR, 2.64; 95% CI, 1.23–5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10–3.57), age (RR, 0.96; 95% CI, 0.92–0.99) and dual nucleoside therapy (RR, 2.69; 95% CI, 1.17–6.15).

Conclusion: The proportion of individuals achieving viral suppression matched results from the developing world. Speaking the same language as site staff and simplified dosing frequency were beneficial. Socio-economic status had no impact on adherence and should not be used as a limitation to ART access.

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The majority of HIV infected individuals live in sub-Saharan Africa. Over 4.7 million people are infected in South Africa alone, approximately one in every five adults [1,2]. South Africa is a middle-income, developing country and until recently, treatment with antiretroviral therapy (ART) on a large scale was considered financially impossible. In 2001, however, the local pricing of triple ART decreased by approximately 75%, and it is now available for less than $1000 per year. A recent out of court settlement between the government and pharmaceutical industry has further encouraged reduced antiretroviral pricing, which will expand access to South Africans receiving health care in the public sector.

Expectation of poor adherence is a major concern in expanding therapy to South Africans, many of whom live in severe poverty [3,4]. A spokesman for USAID encapsulated these assumptions with his statement: ‘Ask Africans to take their drugs at a certain time of day, and they do not know what you are talking about’ [5]. This is concerning because adherence to therapy is a strong predictor of viral load suppression, immune recovery, disease progression, and death [6–13]. There is also the widely held belief that non-adherence to therapy among sub-Saharan Africans will lead to rapid development and spread of HIV drug resistance [3]. In contrast to current expectations of non-adherence, Laurent et al. reported high levels of adherence in Senegal [14.] As yet there are no published studies of objectively measured adherence in resource-limited settings comprising the majority of HIV infected patients.

We set out to measure pill count adherence and virologic suppression in a cohort of semi-urban South Africans living in extreme poverty.

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Eligibility and recruitment

Participants were recruited from the Cape Town AIDS Cohort (CTAC), a group of HIV-positive individuals presenting to University of Cape Town HIV clinics which serve largely indigent populations. Patients were referred to the clinic study site between January 1996 and May 2001 by a broad spectrum of health care workers in the public sector of the wider Cape Town area. All participants were antiretroviral naive and provided written consent to participate in multi-centre phase III clinical trials of combination ART. These studies were approved by the University of Cape Town Research Ethics Committee. Inclusion and exclusion criterion were trial determined. All antiretroviral naive patients who commenced ART on any established study by December 2000 were eligible for adherence monitoring.

ART, routine medical care from the site doctors and nursing staff, and trial-related laboratory monitoring were free. The routine public service hospital system, which requires payment from the patients proportional to their income, was accessed for treatment of intercurrent problems, opportunistic infections or non-trial medication.

A single group education session (usually in English) is held prior to the consenting process and inclusion onto a study. There is no dedicated adherence counseling service, structured adherence support or formal adherence intervention as part of treatment. Patients access the site for 1–2 h every 2 or 3 months. There are no off-site visits by health care staff.

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Demographic and socio-economic data collection

The socio-economic status of participants was assessed using the Cape Metropolitan Council per-suburb composite index which is based on household income (percentage of households earning less than US $1500 per annum), education level (percentage of adults with less than 8 years of schooling), unemployment status (unemployed adults who are actively seeking work as a percentage of all adults), welfare status (percentage of household heads who are single women with three or more children) and overcrowding status (percentage of households with more than 1.5 people per habitable room). The composite index is the sum of these five percentages (maximum 500%) and tends to range from 4 to > 70. A score of > 28.5 correlates well (r, 0.7) with extremely poor conditions of living (shack or informal dwellings with outside tap or public sector housing blocks). An index of 10–28.5 indicates a moderate standard of living (low-cost housing, basic amenities), and an index of < 10 indicates a high standard of living (brick house, full amenities) [15]. For analysis purposes a cut-off of 28.5 was used as the break between poor and reasonable socio-economic circumstances.

Other demographic variables recorded include: age at commencement of therapy, language spoken at home (to question the impact of English-based education processes on adherence), sex, World Health Organisation (WHO) HIV stage, as well as viral load and CD4 cell count at baseline.

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Antiretroviral treatment

Patients were assigned to one of six multi-center phase III studies. Patients in two studies in 1996 were given dual therapy with an additional third concurrent, placebo-controlled and double-blinded drug (placebo versus a non-nuceoside reverse transcriptase inhibitor regimen). In the other four studies patients were given triple therapy regimens.

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Adherence monitoring

Adherence to therapy was assessed using clinic-based pill counts and pharmacy refill data over a period of 48 weeks. All ART was dispensed from the single study site. Patients were provided with more medication than required, i.e. tablets were usually dispensed in multiples of 30, whereas visits were booked in multiples of 28 days. Patients were instructed to return all medication bottles and unused pills at each study visit, but were not told that the returns were to be counted. All tablets of each antiretroviral medication were counted prior to dispensing and upon return. Adherence to therapy was calculated using the formula: (sum of tablets dispensed – sum of tablets returned) / (total tablets prescribed over the 48-week study interval).

Patients who did not complete at least 30 days of ART were excluded from the analysis. Patients who completed at least 30 days of therapy, but who failed to bring any tablet returns over the study period have been included in the analysis and assigned a 0% adherence value. For those who withdrew from the study before 48 weeks, the last data available has been brought forward to be included in the 48-week data analysis.

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Statistical analysis

Chi-squared test was used to compare categorical data and the student's t test was used for continuous variables. Associations were examined at the P < 0.05 level of significance. Logistic regression models were fitted to determine variables predictive of adherence and virologic failure. Only variables which were predictive on univariate analysis (P < 0.05) were included in the multivariate modeling.

Factors used in the univariate model for predicting adherence less than 95% included age (modeled as a continuous variable), language spoken at home (English), three times daily medication dosing, socio- economic status (low), WHO HIV clinical stage (stage 3 or 4), sex (female), and baseline CD4 cell count and viral load.

The univariate models for virologic failure (> 400 HIV RNA copies/ml at 48 weeks) included the baseline viral load, age, daily dosing schedule, adherence and antiretroviral regimen type. Viral load at baseline, age, three times a day regimens, medication-related food restrictions, taking more than 10 tablets a day, adherence < 95% and dual nucleoside therapy were modeled as baseline risk factors.

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Recruitment and retention

A total of 289 patients was eligible for adherence monitoring. Eleven patients (3.8%) were excluded from the analysis because they withdrew consent (six patients) or discontinued therapy due to toxicity (five patients) within 4 weeks of treatment initiation. An additional 36 patients (12.4%) withdrew from the study after the first 4 weeks and were included in the analysis.

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Patient and regimen characteristics

The mean age of the cohort at commencement of ART was 33.4 years (SD, 8.7) and 43% of the cohort was female. Forty-two per cent of the cohort was drawn from poor socio-economic conditions areas (approximately US $1500 per annum per household). A further 20% came from moderate income areas (approximately US $5500 per annum per household). Only 20% of the cohort spoke English as their home language. The majority of the cohort spoke Xhosa, the local African language (48%), or Afrikaans (28%). Demographic and clinical characteristics of the cohort are presented in Table 1.

Table 1
Table 1
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Regimens containing protease inhibitors were used by 120 (41.5%) patients. Ninety-four (32.5%) patients received non-nucleoside based regimens, 30 (10.4%) took triple nucleoside regimens and 45 (15.6%) of the patients, who commenced treatment in 1996, received dual nucleoside reverse transcriptase inhibitor therapy. Fifty-five percent of the cohort took more than 10 tablets a day and 41% had dietary restrictions related to antiretroviral medication.

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Treatment discontinuation

Forty-seven patients (16.2%) discontinued therapy within 48 weeks. Those who discontinued were significantly younger, and had increased viral loads at baseline, with lower CD4 cell counts. Socio-economic status, sex, language spoken at home and WHO stage of HIV illness were not associated with discontinuation.

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Treatment adherence and viral suppression

The median adherence of the cohort up to 48 weeks was 93.5% (mean, 87.2%; n, 278). This includes eight patients who did not return any tablets after continuing therapy beyond 4 weeks and who were assigned 0% adherence. Sixty-three percent of the patients maintained adherence of ≥ 90% to the prescribed tablets. There was no significant difference in adherence to protease regimens compared to non-nucleoside based regimens. The proportion of subjects in each adherence category is illustrated in Fig. 1.

Fig. 1
Fig. 1
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Dosing interval, age and speaking English at home were independently associated with incomplete adherence (Table 2). Medication-related food restrictions (RR, 1.01; 95% CI, 0.63–1.63), taking 10 or more tablets a day (RR, 1.23; 95% CI, 0.77–1.98), low socio-economic status (RR, 1.42; 95% CI, 0.88–2.29) and HIV stage 3 or 4 (RR, 0.90; 95% CI, 0.56–1.45) were not significantly associated with adherence in univariate models and therefore were not included in the multivariate model.

Table 2
Table 2
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Adherence, modeled as a continuous variable, was significantly associated with reduction in viral load at 48 weeks (r, 0.2923; P = 0.001). Of those who reached 48 weeks of therapy (n, 242), 66.1% had a viral load of < 400 HIV RNA copies/ml. This included 70.9% of those on triple therapy and 41.0% of those on dual therapy. For those who were ≥ 95% adherent at 48 weeks, 73.4% had a viral load of < 400 copies/ml compared with only 61.0% of those whose adherence was < 95% (P = 0.018).

Independent predictors of virologic failure included baseline viral load, three times daily dosing, adherence < 95%, age and dual nucleoside therapy. Taking 10 or more tablets a day (RR, 1.11; 95% CI, 0.57–2.17) and medication-related food restrictions (RR, 1.95; 95% CI, 0.95–4.03) were not independently associated with virologic failure at 48 weeks (Table 3).

Table 3
Table 3
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We found that indigent patients recruited from the greater Cape Town area, receiving free therapy on clinical trials, took 93.5% of their medication as measured by clinic-based pill count and, of those on triple therapy, 70.9% maintained a viral load of < 400 copies at 1 year in the absence of formal adherence intervention. This data is consistent with the high levels of self-reported adherence and viral suppression in poor patients receiving ART in Senegal [14]. This level of adherence and viral suppression is similar to or better than that reported in most observational and clinical trial cohorts in developed countries where objective measures of adherence indicate that patients take 70% of their HIV antiretroviral medications (range 53–93%) and rate of viral load suppression is 50% (range 37–72%) on similar regimens [6–10,16–18].

Living in poor socio-economic circumstances, as defined by the Cape Metropolitan Council index, did not impact on adherence to therapy [15]. In contrast to our study, most patients receiving ART in sub-Saharan Africa directly purchase their medications and pay for the cost of monitoring which can be a significant barrier to sustained treatment adherence [19]. Our results suggest that poor patients in sub-Saharan Africa can have successful treatment outcomes when the financial barriers to treatment are removed.

Three times daily therapy was the strongest predictor for both poor adherence and virologic failure in the multivariate analyses. Food restrictions on medication taking and absolute tablet count did not impact on adherence in this cohort and only predicted poor virologic outcomes at a univariate level. Several other studies have also shown that the best improvement in adherence comes with the reduction of dosing frequency from three to two times a day, but have also shown a negative effect of increasing tablet burden on adherence, which this study did not [20,21].

Increasing age was found to correlate with a higher likelihood of remaining on therapy for 48 weeks, as well as improved adherence and virological outcomes. This has been noted in recent literature and is particularly relevant given the rapid increase in HIV seroprevalence in young (19–25-year-old) South Africans [18,22,23].

The home language of each patient was collected as a demographic factor on the hypothesis that patients speaking the same language as the site staff would have an adherence advantage compared to those who were being educated in a second language. People who spoke English, did appear have an adherence benefit. This was unrelated to socio-economic status.

Adherence above 95% to treatment regimens predited virological success. Other factors which impacted on virologic outcome included baseline viral load and regimen type. We noted decreased virologic success with dual nucleoside therapy. Increased viral load at baseline reduced the likelihood of successful viral suppression after 1 year. These factors have been noted to impact similarly elsewhere [18,24].

In this study, clinical stage of HIV at commencement of therapy did not predict adherence, whereas this has been previously reported as a significant predictor [3,20]. Individuals with or without AIDS had the same adherence. Patients in this cohort, in view of their poor socio-economic circumstances and the lack of availability of ART in the South African public sector, may have similar adherence because of the global recognition of the lack of other options for therapy.

In this edition of AIDS, Liechty and Bangsberg [25] argue that the anticipated need to deliver ART as directly observed therapy in developing countries may be premature [3,5,26]. Our results which indicate that poor patients in sub-Saharan Africa can achieve high rates of adherence and viral suppression in the absence of formal adherence intervention support this view.

We used clinic-based pill counts as the primary adherence measure. Whilst there are other measures of adherence that may more accurately reflect pill-taking behavior than clinic-based pill counts [7,8,27–30], this was the only practical and objective method that gave consistent, comparable data across different ART trials. Patients were generally not informed that returns were counted, although this information was not purposefully withheld. Tablet counts are widely used as a marker for adherence [8,11,22,28,29,31]. Pill consumption, however, is not directly measured and therefore the data may represent the upper boundary of actual patient adherence. Patients may not bring in all their medications or some may empty (pill dump) their bottles prior to a clinic visit [22,30]. While these possibilities cannot be excluded, the high rate of viral suppression combined with the significant association between adherence and viral load data suggest the tablet counts in this study correlated with actual adherence. Other investigators have also found a close association between similar clinic-based refill data, as a proxy for adherence, and HIV viral load as well as HIV clinical outcomes, including AIDS and death [12,13, 16,32,33].

The decision to enter patients onto therapy in this study was made on clinical and immunologic criteria; however it is possible that there may have been a selection bias towards patients likely to have better adherence than the general population. ART is not widely available in Cape Town, and, out of large numbers of people with HIV, this cohort was motivated enough to warrant referral from their primary care clinic to a secondary hospital. Subjects on trial also received information and encouragement on a regular basis from medical staff and counselors. This may have enhanced adherence and limit more general applicability.

Most subjects completed 48 weeks of therapy. Subjects who actively withdrew from therapy with in the 48 weeks of the study, tended to do so early in therapy. These patients were generally younger and, although they were not clinically more advanced in terms of disease staging, they tended to have more advanced immunologic and virologic disease. This may have resulted in increased adverse events leading to withdrawal through removal of consent, toxicity, or an HIV-related event. Other demographic factors, such as sex, language and socio-economic status, did not differ between those that withdrew and the rest of the cohort, confirming how difficult it is to predict patient behavior [8,9,34,35].

This study demonstrates that the high levels of adherence required to implement successful ART were achieved in an African cohort without formal adherence intervention. Factors impacting on adherence and virologic outcomes elsewhere were similarly reflected in this cohort. Clinical and virologic benefits were maintained after 1 year. Most importantly, low socio-economic status was not a barrier to success. Individuals with HIV disease, who could potentially benefit from ART, should not be denied access based on otherwise unsubstantiated expectations of poor adherence.

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Sponsorship: M. B. was partially funded by a grant from the BMS ‘Secure-The-Future’ fund. D. B. received funding from The Doris Duke Charitable Foundation.

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AIDS and Behavior
The price of adherence: Qualitative findings from HIV positive individuals purchasing fixed-dose combination generic HIV antiretroviral therapy in Kampala, Uganda
Crane, JT; Kawuma, A; Oyugi, JH; Byakika, JT; Moss, A; Bourgois, P; Bangsberg, DR
AIDS and Behavior, 10(4): 437-442.
American Journal of Health Behavior
Older adult medication compliance: Integrated review of randomized controlled trials
Russell, CL; Conn, VS; Jantarakupt, P
American Journal of Health Behavior, 30(6): 636-650.

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda
Weidle, PJ; Wamai, N; Solberg, P; Liechty, C; Sendagala, S; Were, W; Mermin, J; Buchacz, K; Behumbiize, P; Ransom, RL; Bunnell, R
Lancet, 368(): 1587-1594.
Tropical Medicine & International Health
A 84-month follow up of adherence to HAART in a cohort of adult Senegalese patients
Etard, JF; Laniece, I; Fall, MBK; Cilote, V; Blazejewski, L; Diop, K; Desclaux, A; Ecochard, R; Ndoye, I; Delaporte, E
Tropical Medicine & International Health, 12(): 1191-1198.
Tropical Medicine & International Health
Adherence to antiretroviral therapy in Africa: how high is it really?
Jaffar, S; Munderi, P; Grosskurth, H
Tropical Medicine & International Health, 13(9): 1096-1097.
Jama-Journal of the American Medical Association
Adherence to antiretroviral therapy in sub-Saharan Africa and North America - A meta-analysis
Mills, EJ; Nachega, JB; Buchan, I; Orbinski, J; Attaran, A; Singh, S; Rachlis, B; Wu, P; Cooper, C; Thabane, L; Wilson, K; Guyatt, GH; Bangsberg, DR
Jama-Journal of the American Medical Association, 296(6): 679-690.

HIV Medicine
Characteristics and response to antiretroviral therapy of HIV-1-infected patients born in Africa and living in France
Breton, G; Lewden, C; Spire, B; Salmon, D; Brun-Vezinet, F; Duong, M; Allavena, C; Leport, C; Salamon, R
HIV Medicine, 8(3): 164-170.

International Journal of Std & AIDS
Efficacy of antiretroviral therapy in Africa: effect on immunological and virological outcome measures a meta-analysis
Hammond, R; Harry, TC
International Journal of Std & AIDS, 19(5): 291-296.
Archives of Internal Medicine
Cost-effectiveness of HIV monitoring strategies in resource-limited settings - A Southern African analysis
Bendavid, E; Young, SD; Katzenstein, DA; Bayoumi, AM; Sanders, GD; Owens, DK
Archives of Internal Medicine, 168(): 1910-1918.

Drug resistance and adherence to HIV/AIDS antiretroviral treatment: against a double standard between the north and the south
Moatti, JP; Spire, B; Kazatchkine, M
AIDS, 18(): S55-S61.
AIDS Patient Care and Stds
Influence of prior antiretroviral experience on adherence and responses to new highly active antiretroviral therapy regimens
Horberg, M; Silverberg, M; Hurley, L; Delorenze, G; Quesenberry, C
AIDS Patient Care and Stds, 22(4): 301-312.
Plos Medicine
Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study
Ware, NC; Idoko, J; Kaaya, S; Biraro, IA; Wyatt, MA; Agbaji, O; Chalamilla, G; Bangsberg, DR
Plos Medicine, 6(1): 39-47.
ARTN e1000011
Bmc Pediatrics
Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study
Davies, MA; Boulle, A; Fakir, T; Nuttall, J; Eley, B
Bmc Pediatrics, 8(): -.
Lancet Infectious Diseases
Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review
Barth, RE; van der Loeff, MFS; Schuurman, R; Hoepelmon, AIM; Wensing, AMJ
Lancet Infectious Diseases, 10(3): 155-166.

Bulletin of the World Health Organization
Prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome in resource-limited settings
Hogan, DR; Salomon, JA
Bulletin of the World Health Organization, 83(2): 135-143.

Samj South African Medical Journal
The effects of a language barrier in a South African district hospital
Schlemmer, A; Mash, B
Samj South African Medical Journal, 96(): 1084-1087.

Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia
Ferradini, L; Laureillard, D; Prak, N; Ngeth, C; Fernandez, M; Pinoges, L; Puertas, G; Taburet, AM; Ly, N; Rouzioux, C; Balkan, S; Quillet, C; Delfraissy, JF
AIDS, 21(): 2293-2301.

Plos Medicine
Rationing antiretroviral therapy for HIV/AIDS in Africa: Choices and consequences
Rosen, S; Sanne, I; Collier, A; Simon, JL
Plos Medicine, 2(): 1098-1104.
ARTN e303
Jaids-Journal of Acquired Immune Deficiency Syndromes
Examining theoretic models of adherence for validity in resource-limited settings - A heuristic approach
Ware, NC; Wyatt, MA
Jaids-Journal of Acquired Immune Deficiency Syndromes, 43(): S18-S22.

Tropical Medicine & International Health
Migrants' access to antiretroviral therapy in Thailand
Saether, ST; Chawphrae, U; Zaw, MM; Keizer, C; Wolffers, I
Tropical Medicine & International Health, 12(8): 999-1008.
Patient Education and Counseling
"Tell me so I know you understand": Pharmacists' verification of patients' comprehension of antiretroviral dosage instructions in a cross-cultural context
Watermeyer, J; Penn, C
Patient Education and Counseling, 75(2): 205-213.
Tropical Medicine & International Health
The impact of gender and income on survival and retention in a South African antiretroviral therapy programme
Cornell, M; Myer, L; Kaplan, R; Bekker, LG; Wood, R
Tropical Medicine & International Health, 14(7): 722-731.
International Journal of Epidemiology
Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia
Chi, BH; Cantrell, RA; Zulu, I; Mulenga, LB; Levy, JW; Tambatamba, BC; Reid, S; Mwango, A; Mwinga, A; Bulterys, M; Saag, MS; Stringer, JSA
International Journal of Epidemiology, 38(3): 746-756.
American Journal of Public Health
Brazil and access to HIV/AIDS drugs: A question of human rights and public health
Galvao, J
American Journal of Public Health, 95(7): 1110-1116.
Plos Medicine
Steps on the critical path: Arresting HIV/AIDS in developing countries
Gerberding, J
Plos Medicine, 1(1): 14-16.
ARTN e10
Adherence as therapeutic citizenship: impact of the history of access to antiretroviral drugs on adherence to treatment
Nguyen, VK; Ako, CY; Niamba, P; Sylla, A; Tiendrebeogo, I
AIDS, 21(): S31-S35.

AIDS and Behavior
Longitudinal Antiretroviral Adherence in HIV plus Ugandan Parents and Their Children Initiating HAART in the MTCT-Plus Family Treatment Model: Role of Depression in Declining Adherence Over Time
Byakika-Tusiime, J; Crane, J; Oyugi, JH; Ragland, K; Kawuma, A; Musoke, P; Bangsberg, DR
AIDS and Behavior, 13(): S82-S91.
Tropical Medicine & International Health
Enhancing adherence to antiretroviral therapy at the HIV clinic in resource constrained countries; the Tanzanian experience
Mugusi, F; Mugusi, S; Bakari, M; Hejdemann, B; Josiah, R; Janabi, M; Aboud, S; Aris, E; Swai, H; Mhalu, F; Biberfeld, G; Pallangyo, K; Sandstrom, E
Tropical Medicine & International Health, 14(): 1226-1232.
Clinical Infectious Diseases
Efficacy of antiretroviral therapy programs in resource-poor settings: A meta-analysis of the published literature
Ivers, LC; Kendrick, D; Doucette, K
Clinical Infectious Diseases, 41(2): 217-224.

Southern African Journal of HIV Medicine
The utility of pharmacy dispensing data for art programme evaluation and early identification of patient loss to follow-up
Wood, R; Kaplan, R; Bekker, LG; Brown, S; Rivett, U
Southern African Journal of HIV Medicine, (): 46-+.

Bmc Public Health
Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia
Amberbir, A; Woldemichael, K; Getachew, S; Girma, B; Deribe, K
Bmc Public Health, 8(): -.
ARTN 265
Statistics in Medicine
Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort
Tournoud, M; Etard, JF; Ecochard, R; DeGruttola, V
Statistics in Medicine, 29(1): 14-32.
British Medical Journal
Antiretroviral therapy in Africa
Stevens, W; Kaye, S; Corrah, T
British Medical Journal, 328(): 280-282.

Jama-Journal of the American Medical Association
Treatment of HIV/AIDS - Do the dilemmas only increase?
Sande, MA; Ronald, A
Jama-Journal of the American Medical Association, 292(2): 266-268.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Antiretroviral therapy in resource-poor settings - Decreasing barriers to access and promoting adherence
Mukherjee, JS; Ivers, L; Leandre, F; Farmer, P; Behforouz, H
Jaids-Journal of Acquired Immune Deficiency Syndromes, 43(): S123-S126.

Tropical Medicine & International Health
Risk factors for treatment denial and loss to follow-up in an antiretroviral treatment cohort in Kenya
Karcher, H; Omondi, A; Odera, J; Kunz, A; Harms, G
Tropical Medicine & International Health, 12(5): 687-694.
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV
Factors associated with self-reported adherence to antiretroviral therapy in a Tanzanian setting
Watt, MH; Maman, S; Golin, CE; Earp, JA; Eng, E; Bangdiwala, SI; Jacobson, M
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV, 22(3): 381-389.
Jaids-Journal of Acquired Immune Deficiency Syndromes
International scale-up for antiretroviral treatment - Where does prevention fit?
Valdiserri, RO
Jaids-Journal of Acquired Immune Deficiency Syndromes, 37(): S138-S141.

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment
Ferradini, L; Jeannin, A; Pinoges, L; Izopet, J; Odhiambo, D; Mankhambo, L; Karungi, G; Szumilin, E; Balandine, S; Fedida, G; Carrieri, MP; Spire, B; Ford, N; Tassie, JM; Guerin, PI; Brasher, C
Lancet, 367(): 1335-1342.

AIDS treatment: Staying the course
Check, E
Nature, 442(): 617-619.
Bmc Public Health
"That is why I stopped the ART": Patients' & providers' perspectives on barriers to and enablers of HIV treatment adherence in a South African workplace programme
Dahab, M; Charalambous, S; Hamilton, R; Fielding, K; Kielmann, K; Churchyard, GJ; Grant, AD
Bmc Public Health, 8(): -.
International Journal of Std & AIDS
Adherence to HIV antiretroviral therapy in HIV plus Ugandan patients purchasing therapy
Byakika-Tusiime, J; Oyugi, JH; Tumwikirize, WA; Katabira, ET; Mugyenyi, PN; Bangsberg, DR
International Journal of Std & AIDS, 16(1): 38-41.

Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design
Lawn, SD; Myer, L; Orrell, C; Bekker, LG; Wood, R
AIDS, 19(): 2141-2148.

Plos Medicine
How to take HIV antiretroviral medications on time without a watch in rural Uganda
Maier, M; Bwana, M; Emenyonu, N; Pepper, L; Bangsberg, DR
Plos Medicine, 3(3): 411-412.
ARTN e161
Bulletin of the World Health Organization
Antiretroviral treatment roll-out in a resource-constrained setting: capitalizing on nursing resources in Botswana
Miles, K; Clutterbuck, DJ; Seitio, O; Sebego, M; Riley, A
Bulletin of the World Health Organization, 85(7): 555-560.
Health & Place
"They (ARVs) are my life, without them I'm nothing"-experiences of patients attending a HIV/AIDS clinic in Johannesburg, South Africa
Gilbert, L; Walker, L
Health & Place, 15(4): 1123-1129.
Nature Medicine
Antiretroviral treatment for HIV infection in developing countries: an attainable new paradigm
Moatti, JP; N'Doye, I; Hammer, SM; Hale, P; Kazatchkine, M
Nature Medicine, 9(): 1449-1452.
Samj South African Medical Journal
Tuberculosis control in South Africa - will HAART help?
Lawn, SD; Wood, R
Samj South African Medical Journal, 96(6): 502-+.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Development and assessment of an innovative culturally sensitive educational Videotape to improve adherence to highly active antiretroviral therapy in Soweto, South Africa
Wong, IY; Lawrence, NV; Struthers, H; McIntyre, J; Friedland, GH
Jaids-Journal of Acquired Immune Deficiency Syndromes, 43(): S142-S148.

No room for complacency about adherence to antiretroviral therapy in sub-Saharan Africa
Gill, CJ; Hamer, DH; Simon, JL; Thea, DA; Sabin, LL
AIDS, 19(): 1243-1249.

AIDS Patient Care and Stds
Barriers to Sustaining Antiretroviral Treatment in Kisesa, Tanzania: A Follow-Up Study to Understand Attrition from the Antiretroviral Program
Roura, M; Busza, J; Wringe, A; Mbata, D; Urassa, M; Zaba, B
AIDS Patient Care and Stds, 23(3): 203-210.
Presse Medicale
HIV management in Africa
Tubiana, R
Presse Medicale, 34(): 1597-1604.

Clinical Infectious Diseases
Universal access to antiretroviral therapy: When, not if
Carpenter, CCJ
Clinical Infectious Diseases, 42(2): 260-261.

Medecine Et Maladies Infectieuses
Observance of antiretroviral treatments: African specificities
Eholie, SP; N'Dour, CT; Cisse, M; Bissagnene, E; Girard, PM
Medecine Et Maladies Infectieuses, 36(9): 443-448.
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV
Establishing a workplace antiretroviral therapy programme in South Africa
Charalambous, S; Grant, AD; Day, JH; Pemba, L; Chaisson, RE; Kruger, P; Martin, D; Wood, R; Brink, B; Churchyard, GJ
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV, 19(1): 34-41.
Cochrane Database of Systematic Reviews
Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS (Review)
Rueda, S; Park-Wyllie, LY; Bayoumi, AM; Tynan, AM; Antoniou, TA; Rourke, SB; Glazier, RH
Cochrane Database of Systematic Reviews, (3): -.
ARTN CD001442
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV
Hunger, waiting time and transport costs: Time to confront challenges to ART adherence in Africa
Hardon, AP; Akurut, D; Comoro, C; Ekezie, C; Irunde, HF; Gerrits, T; Kglatwane, J; Kinsman, J; Kwasa, R; Maridadi, J; Moroka, TM; Moyo, S; Nakiyemba, A; Nsimba, S; Ogenyi, R; Oyabba, T; Temu, F; Laing, R
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV, 19(5): 658-665.
South African Journal of Psychology
Adherence to antiretroviral therapy in the context of the national roll-out in South Africa: Defining a research agenda for psychology
Kagee, A
South African Journal of Psychology, 38(2): 413-428.

Bmc Medicine
Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules
le Roux, SM; Cotton, MF; Golub, JE; le Roux, DM; Workman, L; Zar, HJ
Bmc Medicine, 7(): -.
Samj South African Medical Journal
Expanding access to antiretroviral therapy through the public sector - the challenge of retaining patients in long-term primary care
Myer, L; El-Sadr, W
Samj South African Medical Journal, 94(4): 273-274.

Journal of Infectious Diseases
The extraordinary hope of Antiretroviral therapy in South Africa (even for patients with tuberculosis or Kaposi sarcoma!)
Flanigan, TP; Campbell, T; Harwell, J; Kumarasamy, N
Journal of Infectious Diseases, 191(3): 321-323.

AIDS Patient Care and Stds
Safer sexual behaviors after 12 months of antiretroviral treatment in Mombasa, Kenya: A prospective cohort
Luchters, S; Sarna, A; Geibel, S; Chersich, MF; Munyao, P; Kaai, S; Mandaliya, KN; Shikely, KS; Rutenberg, N; Temmerman, M
AIDS Patient Care and Stds, 22(7): 587-594.
Plos One
Adherence Support Workers: A Way to Address Human Resource Constraints in Antiretroviral Treatment Programs in the Public Health Setting in Zambia
Torpey, KE; Kabaso, ME; Mutale, LN; Kamanga, MK; Mwango, AJ; Simpungwe, J; Suzuki, C; Mukadi, YD
Plos One, 3(5): -.
ARTN e2204
Antiviral Therapy
Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa
Van der Borght, SF; Clevenbergh, P; Rijckborst, H; Nsalou, P; Onyia, N; Lange, JM; de Wit, TFR; van der Loeff, MFS
Antiviral Therapy, 14(1): 63-74.

Social Science & Medicine
Public-sector ART in the Free State Province, South Africa: Community support as an important determinant of outcome
Wouters, E; Van Damme, W; Van Loon, F; van Rensburg, D; Meulemans, H
Social Science & Medicine, 69(8): 1177-1185.
Revista Panamericana De Salud Publica-Pan American Journal of Public Health
Assessing HIV resistance in developing countries: Brazil as a case study
Petersen, ML; Boily, MC; Bastos, FI
Revista Panamericana De Salud Publica-Pan American Journal of Public Health, 19(3): 146-156.

International Archives of Allergy and Immunology
HIV/AIDS in Central Africa: Pathogenesis, immunological and medical issues
Sibanda, EN; Stanczuk, G; Kasolo, F
International Archives of Allergy and Immunology, 132(3): 183-195.
AIDS Research and Human Retroviruses
Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa
Nachega, JB; Stein, DM; Lehman, DA; Hlatshwayo, D; Mothopeng, R; Chaisson, RE; Karstaedt, AS
AIDS Research and Human Retroviruses, 20(): 1053-1056.

How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control
Lawn, SD; Bekker, LG; Wood, R
AIDS, 19(): 1113-1124.

AIDS Patient Care and Stds
Barriers to accessing antiretroviral therapy in Kisesa, Tanzania: A qualitative study of early rural referrals to the national program
Mshana, GH; Wamoyi, J; Busza, J; Zaba, B; Changalucha, J; Kaluvya, S; Urassa, M
AIDS Patient Care and Stds, 20(9): 649-657.

Long-term psychosocial challenges for people living with HIV: let's not forget the individual in our global response to the pandemic
Remien, RH; Mellins, CA
AIDS, 21(): S55-S63.

AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV
Community-based follow-up for late patients enrolled in a district-wide programme for antiretroviral therapy in Lusaka, Zambia
Krebs, DW; Chi, BH; Mulenga, Y; Morris, M; Cantrell, RA; Mulenga, L; Levy, J; Sinkala, M; Stringer, JSA
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV, 20(3): 311-317.
Journal of Antimicrobial Chemotherapy
Costs associated with combination antiretroviral therapy in HIV-infected patients
Yazdanpanah, Y
Journal of Antimicrobial Chemotherapy, 53(4): 558-561.
Clinical Infectious Diseases
Comparative evaluation of adherence to antiretroviral therapy in sub-Saharan African native HIV-infected patients in France and Africa
Sellier, P; Clevenbergh, P; Ljubicic, L; Simoneau, G; Evans, J; Delcey, V; Diemer, M; Bendenoun, M; Mouly, S; Bergmann, JF
Clinical Infectious Diseases, 43(5): 654-657.

Plos Medicine
Public-health and individual approaches to antiretroviral therapy: Township South Africa and Switzerland compared
Keiser, O; Orrell, C; Egger, M; Wood, R; Brinkhof, MWG; Furrer, H; van Cutsem, G; Ledergerber, B; Boulle, A
Plos Medicine, 5(7): 1102-1111.
ARTN e148
African patients adhere well to anti-HIV regimens
Oransky, I
Lancet, 362(): 882.

Adherence without access to antiretroviral therapy in sub-Saharan Africa?
Bangsberg, DR; Ware, N; Simoni, JM
AIDS, 20(1): 140-141.

PDF (947)
Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa
Goemaere, E; Coetzee, D; Hildebrand, K; Boulle, A; Maartens, G; Louis, F; Labatala, V; Reuter, H; Ntwana, N
AIDS, 18(6): 887-895.

PDF (110)
Outcomes after virologic failure of first-line ART in South Africa
Murphy, RA; Sunpath, H; Lu, Z; Chelin, N; Losina, E; Gordon, M; Ross, D; Ewusi, AD; Matthews, LT; Kuritzkes, DR; Marconi, VC; for the South Africa Resistance Cohort Study Team,
AIDS, 24(7): 1007-1012.
PDF (131) | CrossRef
Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda
Kityo, C; Mugyenyi, P; Quinn, TC; Bangsberg, DR; Oyugi, JH; Byakika-Tusiime, J; Ragland, K; Laeyendecker, O; Mugerwa, R
AIDS, 21(8): 965-971.
PDF (112) | CrossRef
Initiating highly active antiretroviral therapy in sub-Saharan Africa: an assessment of the revised World Health Organization scaling-up guidelines
Badri, M; Bekker, L; Orrell, C; Pitt, J; Cilliers, F; Wood, R
AIDS, 18(8): 1159-1168.

PDF (151)
Randomized controlled trial of trained patient-nominated treatment supporters providing partial directly observed antiretroviral therapy
Nachega, JB; Chaisson, RE; Goliath, R; Efron, A; Chaudhary, MA; Ram, M; Morroni, C; Schoeman, H; Knowlton, AR; Maartens, G
AIDS, 24(9): 1273-1280.
PDF (198) | CrossRef
Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa
Lawn, SD; Harries, AD; Anglaret, X; Myer, L; Wood, R
AIDS, 22(15): 1897-1908.
PDF (340) | CrossRef
Therapeutic Drug Monitoring
Determination of Nevirapine and Efavirenz in Plasma Using GC/MS in Selected Ion Monitoring Mode
Lemmer, P; Schneider, S; Schuman, M; Omes, C; Arendt, V; Tayari, J; Fundira, L; Wennig, R
Therapeutic Drug Monitoring, 27(4): 521-525.
PDF (213) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Brief Report: Effectiveness of Combination Antiretroviral Therapy on Survival and Opportunistic Infections in a Developing World Setting: An Observational Cohort Study
Tabet, SR; Corey, DM; Kim, HW; Salazar, R; Illescas, R; Villena, J; Gutierrez, L; Sanchez, J
JAIDS Journal of Acquired Immune Deficiency Syndromes, 44(4): 451-455.
PDF (126) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Predictors of Adherence to Antiretroviral Therapy in Rural Zambia
Carlucci, JG; Kamanga, A; Sheneberger, R; Shepherd, BE; Jenkins, CA; Spurrier, J; Vermund, SH
JAIDS Journal of Acquired Immune Deficiency Syndromes, 47(5): 615-622.
PDF (318) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Response to Zidovudine/Didanosine-Containing Combination Antiretroviral Therapy Among HIV-1 Subtype C-Infected Adults in Botswana: Two-Year Outcomes from a Randomized Clinical Trial
Bussmann, H; Wester, CW; Thomas, A; Novitsky, V; Okezie, R; Muzenda, T; Gaolathe, T; Ndwapi, N; Mawoko, N; Widenfelt, E; Moyo, S; Musonda, R; Mine, M; Makhema, J; Moffat, H; Essex, M; DeGruttola, V; Marlink, RG
JAIDS Journal of Acquired Immune Deficiency Syndromes, 51(1): 37-46.
PDF (158) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Adherence to Antiretroviral Therapy Assessed by Drug Level Monitoring and Self-Report in Cameroon
Kouanfack, C; Laurent, C; Peytavin, G; Ciaffi, L; Ngolle, M; Nkene, YM; Essomba, C; Calmy, A; Mpoudi-Ngolé, E; Delaporte, E; Koulla-Shiro, S; for the French National Agency for Research on AIDS 1274 Study Group,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 48(2): 216-219.
PDF (65) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Priorities for Antiretroviral Therapy Research in Sub-Saharan Africa: A 2002 Consensus Conference in Zambia
Zulu, I; Schuman, P; Musonda, R; Chomba, E; Mwinga, K; Sinkala, M; Chisembele, M; Mwaba, P; Kasonde, D; Vermund, SH
JAIDS Journal of Acquired Immune Deficiency Syndromes, 36(3): 831-834.

PDF (66)
JAIDS Journal of Acquired Immune Deficiency Syndromes
Field Adherence to Highly Active Antiretroviral Therapy in HIV-Infected Adults in Abidjan, Côte d'Ivoire
Eholié, S; Tanon, A; Polneau, S; Ouiminga, M; Djadji, A; Kangah-Koffi, C; Diakité, N; Anglaret, X; Kakou, A; Bissagnené, E
JAIDS Journal of Acquired Immune Deficiency Syndromes, 45(3): 355-358.
PDF (76) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Patterns of Individual and Population-Level Adherence to Antiretroviral Therapy and Risk Factors for Poor Adherence in the First Year of the DART Trial in Uganda and Zimbabwe
Muyingo, SK; Walker, AS; Reid, A; Munderi, P; Gibb, DM; Ssali, F; Levin, J; Katabira, E; Gilks, C; Todd, J; the DART Trial Team,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 48(4): 468-475.
PDF (200) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Multiple Validated Measures of Adherence Indicate High Levels of Adherence to Generic HIV Antiretroviral Therapy in a Resource-Limited Setting
Oyugi, JH; Byakika-Tusiime, J; Charlebois, ED; Kityo, C; Mugerwa, R; Mugyenyi, P; Bangsberg, DR
JAIDS Journal of Acquired Immune Deficiency Syndromes, 36(5): 1100-1102.

PDF (59)
JAIDS Journal of Acquired Immune Deficiency Syndromes
Short- and Long-Term Efficacy of Modified Directly Observed Antiretroviral Treatment in Mombasa, Kenya: A Randomized Trial
Kaai, S; Mandaliya, KN; Shikely, KS; Temmerman, M; Rutenberg, N; Sarna, A; Luchters, S; Geibel, S; Chersich, MF; Munyao, P
JAIDS Journal of Acquired Immune Deficiency Syndromes, 48(5): 611-619.
PDF (160) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Adherence to Highly Active Antiretroviral Therapy Assessed by Pharmacy Claims Predicts Survival in HIV-Infected South African Adults
Nachega, JB; Hislop, M; Dowdy, DW; Lo, M; Omer, SB; Regensberg, L; Chaisson, RE; Maartens, G
JAIDS Journal of Acquired Immune Deficiency Syndromes, 43(1): 78-84.
PDF (257) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Expanding Antiretroviral Options in Resource-Limited Settings-A Cost-Effectiveness Analysis
Bendavid, E; Wood, R; Katzenstein, DA; Bayoumi, AM; Owens, DK
JAIDS Journal of Acquired Immune Deficiency Syndromes, 52(1): 106-113.
PDF (141) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Modeling the Impact of a Partially Effective HIV Vaccine on HIV Infection and Death Among Women and Infants in South Africa
Amirfar, S; Hollenberg, JP; Abdool Karim, SS
JAIDS Journal of Acquired Immune Deficiency Syndromes, 43(2): 219-225.
PDF (390) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
A Pilot Study of Food Supplementation to Improve Adherence to Antiretroviral Therapy Among Food-Insecure Adults in Lusaka, Zambia
Cantrell, RA; Sinkala, M; Megazinni, K; Lawson-Marriott, S; Washington, S; Chi, BH; Tambatamba-Chapula, B; Levy, J; Stringer, EM; Mulenga, L; Stringer, JS
JAIDS Journal of Acquired Immune Deficiency Syndromes, 49(2): 190-195.
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The Pediatric Infectious Disease Journal
Electronic Measurement of Adherence to Pediatric Antiretroviral Therapy in South Africa
Müller, AD; Bode, S; Myer, L; Roux, P; von Steinbüchel, N
The Pediatric Infectious Disease Journal, 27(3): 257-262.
PDF (415) | CrossRef
Back to Top | Article Outline

antiretroviral therapy; Africa; adherence; viral load; socio-economic status

© 2003 Lippincott Williams & Wilkins, Inc.


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