Prevalence of drug resistance mutations and HIV type 1 subtypes in an HIV type 1-infected cohort in rural Tanzania.

The development of resistance mutations in drug-targeted HIV-1 genes compromises the success of antiretroviral therapy (ART) programs. Genotyping of these mutations enables adjusted therapeutic decisions both at the individual and population level. We investigated over time the prevalence of HIV-1 primary drug resistance mutations in treatment-naive patients and described the HIV-1 subtype distribution in a cohort in rural Tanzania at the beginning of the ART rollout in 2005-2007 and later in 2009. Viral RNA was analyzed in 387 baseline plasma samples from treatment-naive patients over a period of 5 years. The reverse transcriptase (RT) and protease genes were reversely transcribed, polymerase chain reaction (PCR) amplified, and directly sequenced to identify HIV-1 subtypes and single nucleotide polymorphisms associated with drug resistance (DR-SNPs). The prevalence of major DR-SNPs in 2005-2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. Initial frequencies of subtypes C, A, D, and recombinants were 43%, 32%, 18%, and 7%, respectively. Later similar frequencies were found except for the recombinants, which were found twice as often (15%), highlighting the subtype diversity and a relatively stable subtype frequency in the area. DR-SNPs were found at initiation of the cohort despite very low previous ART use in the area. Statistically, frequencies of major mutations did not change significantly over the studied 5-year interval. These mutations could reflect primary resistances and may indicate a possible risk for treatment failure.

Improved antiretroviral treatment outcome in a rural African setting is associated with cART initiation at higher CD4 cell counts and better general health condition.

BACKGROUND: Data on combination antiretroviral therapy (cART) in remote rural African regions is increasing. METHODS: We assessed prospectively initial cART in HIV-infected adults treated from 2005 to 2008 at St. Francis Designated District Hospital, Ifakara, Tanzania. Adherence was assisted by personal adherence supporters. We estimated risk factors of death or loss to follow-up by Cox regression during the first 12 months of cART. RESULTS: Overall, 1,463 individuals initiated cART, which was nevirapine-based in 84.6%. The median age was 40 years (IQR 34-47), 35.4% were males, 7.6% had proven tuberculosis. Median CD4 cell count was 131 cells/µl and 24.8% had WHO stage 4. Median CD4 cell count increased by 61 and 130 cells/µl after 6 and 12 months, respectively. 215 (14.7%) patients modified their treatment, mostly due to toxicity (56%), in particular polyneuropathy and anemia. Overall, 129 patients died (8.8%) and 189 (12.9%) were lost to follow-up. In a multivariate analysis, low CD4 cells at starting cART were associated with poorer survival and loss to follow-up (HR 1.77, 95% CI 1.15-2.75, p=0.009; for CD4<50 compared to >100 cells/µl). Higher weight was strongly associated with better survival (HR 0.63, 95% CI 0.51-0.76, p<0.001 per 10 kg increase). CONCLUSIONS: cART initiation at higher CD4 cell counts and better general health condition reduces HIV related mortality in a rural African setting. Efforts must be made to promote earlier HIV diagnosis to start cART timely. More research is needed to evaluate effective strategies to follow cART at a peripheral level with limited technical possibilities.

Impact of a national HIV voluntary counselling and testing (VCT) campaign on VCT in a rural hospital in Tanzania.

OBJECTIVE: To evaluate the impact of a national HIV voluntary counselling and testing (VCT) campaign on presentation to HIV care in a rural population in Tanzania. METHODS: Retrospective analysis of data of the VCT and of the National AIDS Control Programme registers of the St. Francis Designated District Hospital at Ifakara for the two 6-month periods before (2007) and after (2008) the National VCT Campaign. RESULTS: There were 4354 individuals presenting at St. Francis Hospital tested for HIV; 2065 (47.4%) before the VCT Campaign and 2289 (52.6%) afterwards. The overall HIV test positivity was 24.6% and higher in 2007 than in 2008 (26%vs. 23%, P = 0.034). This rate was much higher than the Tanzanian National HIV prevalence of 5.7%. Of 1069 individuals who tested HIV-positive, the proportion of married, divorced or widowed individuals and those who lived further than 10 km from the hospital increased from 2007 to 2008. In 356 HIV-infected persons with available data, the median CD4 cell count increased from 137 to 163 cells/mm(3) (P = 0.058), while the WHO clinical stage was similar in both periods. Enrolling into the National AIDS Control Programme was significantly more common in 2008 (42%vs. 30%, P < 0.001). In a multivariate analysis, the only positive predictor of testing HIV positive when presenting for care after the National VCT Campaign was being married (OR 1.61, 95%CI 1.21-2.15, P = 0.001) or divorced/widowed compared to single (OR 4.58, 95% CI 3.00-8.12, P < 0.001). CONCLUSIONS: Our results suggest that the National VCT Campaign raised awareness and readiness to test for HIV in a remote rural setting and that the HIV-positive test rate is much higher in conjunction with a specific HIV care programme.