Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring.

OBJECTIVES: To describe the resistance mutations selected by a first-line regimen of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring. DESIGN: A substudy of 300 participants from the Development of Antiretroviral Therapy in Africa trial in Uganda and Zimbabwe, which compared managing antiretroviral therapy with and without laboratory monitoring. METHODS: Stored plasma samples from selected time points were assayed retrospectively for HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >1000 copies per milliliter at weeks 24 and 48 were sequenced. RESULTS: The proportion with HIV RNA >1000 copies per milliliter increased from 15% at 24 weeks to 24% at 48 weeks. Eighteen of 31 (58%) genotyped samples at 24 weeks had ≥ 1 major nucleoside reverse transcriptase inhibitor-associated mutations compared with 41 of 47 (87%) at 48 weeks. Excluding 1 nonadherent patient, a mean of 2.0 (95% confidence interval: 1.3 to 2.8) thymidine analogue mutations (TAMs) developed between weeks 24 and 48 among 14 patients with HIV RNA >1000 copies per milliliter at both time points. K65R was detected in 8 of 63 (13%) patients and was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P = 0.30). CONCLUSIONS: A high rate of acquisition of TAMs, but not of K65R, among patients with prolonged viraemia was observed. However, most patients were virologically suppressed at 48 weeks, and long-term clinical and immunological outcomes in the Development of Antiretroviral Therapy in Africa trial were favorable.

Typing of human papillomavirus in Zimbabwean patients with invasive cancer of the uterine cervix.

BACKGROUND: Cervical cancer affects 1 in 2000 Zimbabwean women. We investigated the type-specific distribution of human papillomavirus (HPV) infection in Zimbabwean women with invasive cervical cancer. METHODS: We conducted a descriptive study on 98 women with invasive cervical cancer. The methods used were a nested polymerase chain reaction (PCR) for amplification of HPV-DNA and restriction fragment length polymorphism (RFLP) to characterize the HPV types. RESULTS: HPV-DNA was identified in 97% of the cases. HPV types 16, 33, 18 and 31 were identified in 61%, 39%, 18% and 4% of the patients, respectively. We typed one case each of HPV types 35 and 58. Multiple HPV infections were present in 24%. All patients (n = 3) with adenocarcinoma of the cervix were infected with the HPV. Patients infected with HPV-16 alone presented at a median age of 46 years while those infected with HPV-33 alone presented at 43 years. However, patients coinfected with both HPV-16 and HPV-33 were between 10 and 13 years older (median age of 56 years) than patients with either HPV-16 or HPV-33 as single infections. These differences were marginally significant (p = 0.08) or significant (p = 0.02), respectively. CONCLUSION: We present the first prevalence data on HPV types in patients with cervical cancer in Zimbabwe and show that, provided appropriate techniques are employed, HPV infection can be identified in a majority of the patients. The distribution of HPV types should be taken into consideration in tailoring locally relevant vaccines against HPV.

Detection of human papillomavirus in urine and cervical swabs from patients with invasive cervical cancer.

Despite the high prevalence of both human papillomavirus (HPV) infections and cervical cancer among Zimbabwean women, the ability to test for HPV infection of the uterine cervix is limited by a lack of an easy sample collection method that does not require gynecological examination. The presence of HPVs in urine and cervical swab samples collected from 43 women who presented with invasive cervical cancer was investigated. HPV detection was done by means of degenerate primers in a nested polymerase chain reaction (PCR). Typing of HPVs was done using restriction fragment length polymorphism (RFLP) analysis. HPV was identified and typed in 98% (42/43) of cervical swabs and 72% (31/43) of paired urine samples. HPV type 16 was the most common (25/42, 59%), followed by types: 33 (13/42, 31%), 18 (6/42, 14%), and 31 (1/42, 2%). Type-specific concordance between cervical and urine samples was high (22/28, 79%). Therefore, the HPV types identified in urine samples in most cases represent the same HPV type infecting the cervical epithelium. The results suggest that urine may be a practical sample for testing of HPV urogenital infection. Further research is required before the detection of HPV in urine can be applied in the routine cervical screening programs.